1. Field of the Invention
The present invention relates generally to implantable medical devices and to a method for manufacturing implantable medical devices and depositing and affixing solids onto those devices. More particularly, the present invention relates to an implantable medical device, such as a stent or other intravascular or intraductal medical device, and to a method for depositing and affixing radiopacifiers, radioactive isotopes and or therapeutical chemicals or drugs onto those devices.
2. Description of Related Art
In a typical percutaneous transluminal coronary angioplasty (PTCA) for compressing lesion plaque against the artery wall to dilate the artery lumen, a guiding catheter is percutaneously introduced into the cardiovascular system of a patient through the brachial or femoral arteries and advanced through the vasculature until the distal end is in the ostium. A dilatation catheter having a balloon on the distal end is introduced through the catheter. The catheter is first advanced into the patient""s coronary vasculature until the dilatation balloon is properly positioned across the lesion.
Once in position across the lesion, a flexible, expandable, preformed balloon is inflated to a predetermined size at relatively high pressures to radially compress the atherosclerotic plaque of the lesion against the inside of the artery wall and thereby dilate the lumen of the artery. The balloon is then deflated to a small profile, so that the dilatation catheter can be withdrawn from the patient""s vasculature and blood flow resumed through the dilated artery. While this procedure is typical, it is not the only method used in angioplasty.
In angioplasty procedures of the kind referenced above, restenosis of the artery often develops which may require another angioplasty procedure, a surgical bypass operation, or some method of repairing or strengthening the area. To reduce the likelihood of the development of restenosis and strengthen the area, a physician can implant an intravascular prosthesis, typically called a stent, for maintaining vascular patency. A stent is a device used to hold tissue in place or to provide a support for a vessel to hold it open so that blood flows freely. Statistical data suggests that with certain stent designs, the restenosis rate is significantly less than the overall restenosis rate for non-stented arteries receiving a PTCA procedure.
A variety of devices are known in the art for use as stents, including expandable tubular members, in a variety of patterns, that are able to be crimped onto a balloon catheter, and expanded after being positioned intraluminally on the balloon catheter, and that retain their expanded form. Typically, the stent is loaded and crimped onto the balloon portion of the catheter, and advanced to a location inside the artery at the lesion. The stent is then expanded to a larger diameter, by the balloon portion of the catheter, to implant the stent in the artery at the lesion. Typical stents and stent delivery systems are more fully disclosed in U.S. Pat. No. 5,514,154 (Lau et al.), U.S. Pat. No. 5,507,768 (Lau et al.), and U.S. Pat. No. 5,569,295 (Lam et al.).
Stents are commonly designed for long-term implantation within the body lumen. Some stents are designed for non-permanent implantation within the body lumen. By way of example, several stent devices and methods can be found in commonly assigned and common owned U.S. Pat. No. 5,002,560 (Machold et al.), U.S. Pat. No. 5,180,368 (Garrison), and U.S. Pat. No. 5,263,963 (Garrison et al.).
Patients treated by PTCA procedures, even when implanted with stents, however, may suffer from restenosis, at or near the original site of the stenosis, the coronary vessel collapsing or becoming obstructed by extensive tissue growth, also known as intimal hyperplasia. Clinical studies have indicated that anti-proliferative drug therapy or intravascular low-dose radiation therapy after balloon angioplasty or an atherectomy procedure can prevent or reduce the rate of restenosis caused by intimal hyperplasia.
One approach for performing low-dose intravascular radiotherapy is using a treatment catheter with a low-intensity radiation source. Another approach uses a low-intensity implantable radioactive device such as a radioactive stent with either beta emitting or low energy gamma-emitting radioisotopes. Yet another approach contemplates treating the area of the stenosis over an extended period of time with low dosages of anti-proliferative chemicals or drug compounds.
Intravascular or intraductal implantation of a stent generally involves advancing the stent on a balloon catheter or a similar device to the designated vessel/duct site, properly positioning the stent at the vessel/duct site, and deploying the stent by inflating the balloon which then expands the stent radially against the wall of the vessel/duct. Proper positioning of the stent requires precise placement of the stent at the vessel/duct site to be treated. Visualizing the position and expansion of the stent within a vessel/duct area is usually done using a fluoroscopic or x-ray imaging system.
Where the area of a lesion is to be treated with radiation, the implantable stent is generally made radioactive prior to being inserted into the patient. To make a stent radioactive, a number of techniques are used in the field. For example, a beta-emitting or low energy gamma-emitting radioisotope may be implanted or alloyed into a metal from which the stent is made. The radioisotope may also be coated onto the surface of the stent using an electroplating process. Furthermore, the stent may be made radioactive through neutron activation in a nuclear reactor or similar facility.
Each of these techniques has certain disadvantages including poor and/or non-uniform adhesion of the radioisotope to the surface of the stent, fabrication difficulties with respect to radiation exposure of workers during the manufacturing process, and the risk of generating considerable quantities of undesired isotopes from the neutron activation process which may continue to affect the irradiated tissue long after the desired restenosis treatment period is over. Another significant shortcoming associated with current methods of making a stent radioactive is that these methods are complex and require the performance of many sequential processing steps, which greatly increase the radioactive stent manufacturing cost.
Where the area of the lesion is to be treated using anti-proliferative chemicals or drug compounds, the stent must be coated with the chemical or drug prior to implantation. Such coatings may make the stent difficult to handle, and may complicate implantation of the stent. Further, variations in the thickness of the coating may provide for varying release of the chemical or drug at the lesion site, possible affecting the efficacy of the anti-proliferative effect on the surrounding tissue.
A requirement for any clinically useful stent is that it should have good visibility under fluoroscopic x-ray illumination so that the position of the stent during the implantation procedure is visible to the physician performing the procedure. Since implantable radioactive stents are generally made of metal or metal alloys such as 316L stainless steel or nickel-titanium alloy, such as nitinol, they are not readily visible under fluoroscopic illumination. To make these, and other, non-radioactive, stents manufactured from non-radiopaque materials visible in an x-ray, radiopaque markers are typically attached onto the stent using a number of techniques. One current technique involves applying a coating of a radiopaque marker material, also called radiopacificer material such as gold or tantalum onto the stent, or selected portions of the stent, using an electroplating process. Another technique involves soldering or brazing a radiopaque marker material at specific locations onto the stent. Generally, radiopaque markers are soldered at the longitudinal ends, that is, the most proximal and most distal portions of the stent.
A number of shortcomings or disadvantages are associated with the prior art devices and techniques for attaching radiopaque markers, radioisotopes and chemicals or drugs onto stents or other implantable medical devices. For example, certain conventional radiopaque markers attached onto a stent tend to protrude from the walls of the stent, thus altering the stent profile under fluoroscopy. Other current radiopaque markers that are attached within the surface of the stent may impair the expansion capability of the stent. Still other current methods of attaching radiopaque markers or radioisotopes to the surface of a stent are disadvantageous in that some radiopaque materials and radioisotopes are not compatible with body fluids or tissue and thus must be covered by another material, such as stainless steel, that is compatible with body fluids and tissue. This extra layer of material must be thin enough to avoid unnecessarily thickening the profile of the stent or implantable device, yet must also be thick enough to resist damage during manufacturing, routine handling and implantation of the medical device.
Another disadvantage with current radiopaque marker technology is that, when viewed under fluoroscopic illumination, the radiopaque markers may provide poor or no indication of whether the stent is fully extended. Another significant shortcoming associated with current methods of attaching a radioisotope, radiopaque marker material or drug onto a stent is that these methods can be tedious, imprecise, and require the performance of many sequential processing steps, which greatly increase the stent manufacturing cost.
The invention provides for improved designs of implantable medical devices such as stents and methods for manufacturing same. The implantable medical devices and stents are manufactured from tubular blanks that are formed by inserting a tightly fitting inner tubular member into an outer tubular member. The inner tubular member may include cavities or microdepots formed on the outer surface of the inner tubular member. The cavities or microdepots may be filled with radioactive, radiopaque and/or therapeutic substances. Channels may also be formed on the outer surface of the inner tubular member to connect the cavities or microdepots with a body lumen. The invention also provides methods describing the application of materials to be deposited in or on the microdepots to render the stent or other implantable medical device radioactive, radiopaque, or therapeutic, either in whole or in part. Rendering the implantable medical device radiopaque allows the use of fluoroscopy to assist in placing the implantable medical device or stent at a desired location in the lumen of a vessel or duct.
In one embodiment, the stent or implantable medical device has a plurality of undulating cylindrical elements or rings that are interconnected by connecting elements. The stent or implantable medical device is manufactured by laser cutting a stent pattern from a tubular blank that is formed by tightly inserting an inner tubular member into an outer tubular member. Thus, the resulting stent structure cut from the tubular blank is a composite of the inner and outer tubular members.
In another embodiment, cavities or microdepots may be formed on the outer surface of the inner tubular member by an etching or machining process. The microdepots may be formed over the entire surface of the stent or medical device, or they may be formed in only selected areas of the device, such as in areas adjacent the distal and proximal ends of the device. This embodiment is advantageous in that the microdepots may be distributed on the outer surface of the inner tubular member in such a way that the distribution, or pattern, of the microdepots coincides with the pattern of the stent or implantable medical device structure formed of cylindrical elements and connecting elements. In this manner, the microdepots are contained within the overall wall thickness of the structure of the stent or implantable medical device.
The inclusion of cavities or microdepots on the outer surface of the inner tubular member provides a carrier for materials, such as radioisotopes, radiopaque materials, or therapeutic chemicals or drugs to deposited on the inner tubular member. Radiopaque materials to be deposited on the inner tubular member include materials known in the art of radiopaque markers, such as silver, gold, platinum or tantalum, or other materials that are compatible with implantation in a body lumen or duct and which are visible under fluoroscopy or other body vessel/organ imaging system. Radioactive materials that may be deposited in the cavities or microdepots on the outer surface of the inner tubular member include beta-emitting radioisotopes and gamma-emitting radioisotopes. Therapeutic substances, such as chemicals and drugs may also be deposited in the cavities or microdepots.
The microdepots may be formed over the entire surface of the stent or implantable medical device, or they may be formed in only selected areas of the device, such as in areas adjacent the distal and proximal ends of the device. Even if microdepots are formed over the entire outer surface of the device, the materials to be deposited may be applied to only selected microdepots. For example, radiopaque material may be deposited only in microdepots adjacent the distal and proximal ends of the device. Deposition of radioactive and radiopaque material in microdepots located on the outer surface of the inner tubular member is advantageous in that the radioactive and radiopaque materials are not exposed to the blood or ductal fluid stream flowing through the interior of the stent or implantable medical device. This helps prevent any deleterious effect on the blood or ductal fluid caused by the radioactive and radiopaque material.
In another embodiment, channels may be provided on the outer surface of the inner tubular member extending from the cavities or microdepots to areas of the inner tubular member that will be cut away during processing of the tubular blank. In this manner, pathways between the microdepots and the body or duct lumen in which the stent or implantable medical device is implanted may be provided. These pathways may be sized so as to control the release rate of therapeutic substances deposited in the cavities or microdepots to the lumen.
In one embodiment of a method to manufacture stents or implantable devices in accordance with the invention, an inner tubular member is provided that may include cavities or microdepots formed on its surface. Materials, such as radioisotopes, radiopaque materials or therapeutic substances may be deposited in the cavities or microdepots. In one variation, where the stent or implantable device is intended to deliver a therapeutic substance, channels are cut into the outer surface of the inner tubular member to provide a pathway between the cavities or microdepots and a body lumen to allow for controlled delivery of the therapeutic substance to the body lumen. The completed inner tubular member is inserted into the outer tubular member such that the inner and outer tubular members are in tight fitting engagement. The tubular blank is then mounted in a collet, and the blank may be indexed so that the pattern of microdepots formed on the inner tubular member coincides with a stent or implantable device pattern that is cut into the tubular blank using a suitable computer controlled laser. The laser cutting machinery includes the capability of moving the laser and mounted tubular blank in a programmed manner to cut a desired structural pattern in to the blank. In another variation, the cutting speed and relative movement of the laser and blank are adjusted so that, while heating of the blank by the laser is minimized, local heating at the beam site is allowed to occur and results in thermal bonding of the outer and inner tubular members.
In another embodiment, materials to be deposited in the microdepots are deposited in the microdepots on the outer surface of the inner tubular member by dipping or immersing the inner tubular member into a mixture or solution of material atoms and a suitable solvent or suspension agent. Such a solution or mixture may include, for example, phosphoric acid, Freon or other solvent. In another approach, the material atoms may be suspended in a polymer solution having material characteristics, such as viscosity or wetting properties, that suspends the material atoms in the polymer solution while coating the atoms with the polymer.
The material atoms may be applied to the surface of the inner tubular member using a variety of methods, such as dipping or immersion. The entire inner tubular member may be dipped or immersed either in whole, or in part. For example, only the areas of the inner tubular member adjacent to areas that will become the distal and proximal ends of the stent or implantable medical device when manufacturing is completed may be dipped or immersed in the mixture or solution containing the material atoms.
Alternatively, the mixture or solution containing the material atoms to be deposited may be deposited in the cavities or microdepots of the inner tubular member using micro-injection. In this method, the mixture or solution containing the material atoms is injected into the cavities or microdepots covering the outer surface of the inner tubular member, or the atoms may be injected into cavities or microdepots in selected areas of the inner tubular member.
When the material solution or mixture has coated the inner tubular member, excess material solution or mixture may be removed from the inner tubular member by centrifuging or shaking the inner tubular member. Centrifuging is particularly advantageous, since the centrifugal force assists distribution of the solution across the microdepots and the solution stripped from the inner tubular member may be recycled and reused, thus minimizing loss of material and reducing cost.
In another embodiment of the present invention, the coated inner tubular member may be heated to remove excess solvent or solution and to bind radiopaque material atoms on the surface of the inner tubular member. The heating process may be accomplished using various methods of applying heat in a controlled manner to the inner tubular member, such as using a thermal oven, an inert gas plasma, exposing the coated inner tubular member to an electric arc, or by subjecting the radiopaque atoms coating the inner tubular member to low power exposure from an excimer laser.
In yet another embodiment of the present invention, the material atoms to be deposited may be deposited on the surface of the inner tubular member using an electrodeposition process. In this embodiment, the inner tubular member is attached to a cathode or negative terminal of an electrical current source and dipped or immersed into a positively charged ion mixture or solution of atoms of the material to be deposited. When current flow is initiated, the ions are attracted to the cathode and coat the surface of the inner tubular member.
Other features and advantages of the present invention will become more apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention.